Title

Impairing The Mitochondrial Fission And Fusion Balance: A New Mechanism Of Neurodegeneration

Keywords

Drp1; GTPases; Huntington's disease; Mitofusins; OPA1; Parkin; Parkinson's disease; PINK1

Abstract

Mitochondrial dysfunction is a common characteristic of all neurodegenerative diseases. However, the cause of this dysfunction remains a mystery. Here, we discuss the potential role of mitochondrial fission and fusion in the onset and progression of neurodegenerative diseases. Specifically, we propose that an imbalance in mitochondrial fission and fusion may underlie both familial and sporadic neurodegenerative disorders. There is substantial evidence that links disruption of the mitochondrial fission and fusion equilibrium, resulting in abnormally long or short mitochondria, to neurodegeneration. First, hereditary mutations in the mitochondrial fusion GTPases optic atrophy-1 and mitofusin-2 cause neuropathies in humans. In addition, recent findings report increased mitochondrial fission in Parkinson's disease (PD) models and induction of mitochondrial fission by two proteins, PTEN-induced kinase 1 and parkin, which are mutant in familial forms of PD. Furthermore, mutant huntingtin, the disease-causing protein in Huntington's disease, alters mitochondrial morphology and dynamics. Rotenone, a pesticide and inducer of PD symptoms, and amyloid-β peptide, which is causally linked to Alzheimer's disease, initiate mitochondrial fission. Finally, mitochondrial fission is an early event in ischemic stroke and diabetic neuropathies. In sum, a growing body of research suggests that a better understanding of mitochondrial fission and fusion and the regulatory factors involved may lead to improved treatments and cures for neurodegenerative diseases. © 2008 New York Academy of Sciences.

Publication Date

1-1-2008

Publication Title

Annals of the New York Academy of Sciences

Volume

1147

Number of Pages

283-292

Document Type

Article; Proceedings Paper

Personal Identifier

scopus

DOI Link

https://doi.org/10.1196/annals.1427.030

Socpus ID

57649210194 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/57649210194

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